The Immune System: Innate and Adaptive

Body Defenses
Immunity: Two Intrinsic Defense Systems
• Innate (nonspecific) system responds quickly and consists of:
• First line of defense – intact skin and mucosae prevent entry of
microorganisms
• Second line of defense – antimicrobial proteins, phagocytes, and
other cells
• Inhibit invaders spread throughout the body
• Inflammation is its hallmark and most important mechanism
Immunity: Two Intrinsic Defense Systems
• Adaptive (specific) defense system
• Third line of defense – mounts attack against particular foreign
substances
• Takes longer to react than the innate system
• Works in conjunction with the innate system
Surface Barriers
• Skin, mucous membranes, and their secretions make up the first line
of defense
• Keratin in the skin:
• Presents a formidable physical barrier to most microorganisms
• Is resistant to weak acids and bases, bacterial enzymes, and toxins
• Mucosae provide similar mechanical barriers
Epithelial Chemical Barriers
• Epithelial membranes produce protective chemicals that destroy
microorganisms
• Skin acidity (pH of 3 to 5) inhibits bacterial growth
• Sebum contains chemicals toxic to bacteria
• Stomach mucosae secrete concentrated HCl and protein-digesting
enzymes
• Saliva and lacrimal fluid contain lysozyme
• Mucus traps microorganisms that enter the digestive and respiratory
systems
Respiratory Tract Mucosae
• Mucus-coated hairs in the nose trap inhaled particles
• Mucosa of the upper respiratory tract is ciliated
• Cilia sweep dust- and bacteria-laden mucus away from lower
respiratory passages
Internal Defenses: Cells and Chemicals
• The body uses nonspecific cellular and chemical devices to protect
itself
• Phagocytes and natural killer (NK) cells
• Antimicrobial proteins in blood and tissue fluid
• Inflammatory response enlists macrophages, mast cells, WBCs, and
chemicals
• Harmful substances are identified by surface carbohydrates unique
to infectious organisms
Phagocytes
• Macrophages are the chief phagocytic cells
• Free macrophages wander throughout a region, in search of cellular
debris
• Kupffer cells (liver) and microglia (brain) are fixed macrophages
• Neutrophils become phagocytic when encountering infectious
material
• Eosinophils are weakly phagocytic against parasitic worms
• Mast cells bind and ingest a wide range of bacteria
Mechanism of Phagocytosis
• Microbes adhere to the phagocyte
• Pseudopods engulf the particle (antigen) into a phagosome
• Phagosomes fuse with a lysosome to form a phagolysosome
• Microbes in the phagolysosome are enzymatically digested
• Indigestible and residual material is removed by exocytosis
Natural Killer (NK) Cells
• Cells that can lyse and kill cancer cells and virus-infected cells
• Natural killer cells:
• Are a small, distinct group of large granular lymphocytes
• React nonspecifically and eliminate cancerous and virus-infected
cells
• Kill their target cells by releasing cytolytic chemicals
• Secrete potent chemicals that enhance the inflammatory response
Inflammation: Tissue Response to Injury
• The inflammatory response is triggered whenever body tissues are
injured
• Prevents the spread of damaging agents to nearby tissues
• Disposes of cell debris and pathogens
• Sets the stage for repair processes
• The four cardinal signs of acute inflammation are redness, heat,
swelling, and pain
Inflammatory Response
• Begins with a flood of inflammatory chemicals released into the
extracellular fluid
• Inflammatory mediators:
• Include kinins, prostaglandins (PGs), complement, and cytokines
• Are released by injured tissue, phagocytes, lymphocytes, and mast
cells
• Cause local small blood vessels to dilate, resulting in hyperemia
Inflammatory Response: Vascular Permeability
• Chemicals liberated by the inflammatory response
• Increase the permeability of local capillaries
• Exudate (fluid containing proteins, clotting factors, and antibodies):
• Seeps into tissue spaces causing local edema (swelling)
• The edema contributes to the sensation of pain
Inflammatory Response: Edema
• The surge of protein-rich fluids into tissue spaces (edema):
• Helps to dilute harmful substances
• Brings in large quantities of oxygen and nutrients needed for repair
• Allows entry of clotting proteins, which prevent the spread of
bacteria
Inflammatory Response: Phagocytic Mobilization
• Occurs in four main phases:
• Leukocytosis – neutrophils are released from the bone marrow in
response to leukocytosis-inducing factors released by injured cells
• Margination – neutrophils cling to the walls of capillaries in the
injured area
• Diapedesis – neutrophils squeeze through capillary walls and begin
phagocytosis
• Chemotaxis – inflammatory chemicals attract neutrophils to the
injury site
Antimicrobial Proteins
• Enhance the innate defenses by:
• Attacking microorganisms directly
• Hindering microorganisms’ ability to reproduce
• The most important antimicrobial proteins are:
• Interferon
• Complement proteins
Interferon (IFN)
• Genes that synthesize IFN are activated when a host cell is invaded
by a virus
• Interferon molecules leave the infected cell and enter neighboring
cells
• Interferon stimulates the neighboring cells to activate genes for PKR
(an antiviral protein)
• PKR nonspecifically blocks viral reproduction in the neighboring
cell
Interferon Family
• Interferons are a family of related proteins each with slightly
different physiological effects
• Lymphocytes secrete gamma () interferon, but most other WBCs
secrete alpha () interferon
• Fibroblasts secrete beta () interferon
• Interferons also activate macrophages and mobilize NKs
• FDA-approve alpha IFN is used:
• As an antiviral drug against hepatitis C virus
• To treat genital warts caused by a herpes virus
Complement
• 20 or so proteins that circulate in the blood in an inactive form
• Proteins include C1 through C9, factors B, D, and P, and regulatory
proteins
• Provides a major mechanism for destroying foreign substances in
the body
• Amplifies all aspects of the inflammatory response
• Kills bacteria and certain other cell types (our cells are immune to
complement)
• Enhances the effectiveness of both nonspecific and specific defenses
Complement Pathways
• Complement can be activated by two pathways: classical and
alternative
• Classical pathway is linked to the immune system
• Depends upon the binding of antibodies to invading organisms
• Subsequent binding of C1 to the antigen-antibody complexes
(complement fixation)
• Alternative pathway is triggered by interaction among factors B, D,
and P, and polysaccharide molecules present on microorganisms
• Each pathway involves a cascade in which complement proteins are
activated in an orderly sequence and where each step catalyzes the
next
• Both pathways converge on C3, which cleaves into C3a and C3b
• C3b initiates formation of a membrane attack complex (MAC)
• MAC causes cell lysis by interfering with a cell’s ability to eject
Ca2+
• C3b also causes opsonization, and C3a causes inflammation
Fever
• Abnormally high body temperature in response to invading
microorganisms
• The body’s thermostat is reset upwards in response to pyrogens,
chemicals secreted by leukocytes and macrophages exposed to
bacteria and other foreign substances
• High fevers are dangerous as they can denature enzymes
• Moderate fever can be beneficial, as it causes:
• The liver and spleen to sequester iron and zinc (needed by
microorganisms)
• An increase in the metabolic rate, which speeds up tissue repair
Adaptive (Specific) Defenses
• The adaptive immune system is a functional system that:
• Recognizes specific foreign substances
• Acts to immobilize, neutralize, or destroy them
• Amplifies inflammatory response and activates complement
Adaptive Immune Defenses
• The adaptive immune system is antigen-specific, systemic, and has
memory
• It has two separate but overlapping arms
• Humoral, or antibody-mediated immunity
• Cellular, or cell-mediated immunity
Antigens (Ags)
• Substances that can mobilize the immune system and provoke an
immune response
• The ultimate targets of all immune responses are mostly large,
complex molecules not normally found in the body (nonself)
Complete Antigens
• Important functional properties:
• Immunogenicity – the ability to stimulate proliferation of specific
lymphocytes and antibody production
• Reactivity – the ability to react with the products of the activated
lymphocytes and the antibodies released in response to them
• Complete antigens include foreign protein, nucleic acid, some lipids,
and large polysaccharides
Haptens (Incomplete Antigens)
• Small molecules, such as peptides, nucleotides, and many hormones,
that are not immunogenic but are reactive when attached to protein
carriers
• If they link up with the body’s proteins, the adaptive immune system
may recognize them as foreign and mount a harmful attack (allergy)
• Haptens are found in poison ivy, dander, some detergents, and
cosmetics
Antigenic Determinants
• Only certain parts of an entire antigen are immunogenic
• Antibodies and activated lymphocytes bind to these antigenic
determinants
• Most naturally occurring antigens have numerous antigenic
determinants that:
• Mobilize several different lymphocyte populations
• Form different kinds of antibodies against it
• Large, chemically-simple molecules (e.g., plastics) have little or no
immunogenicity
Self-Antigens: MHC Proteins
• Our cells are dotted with protein molecules (self-antigens) that
are not antigenic to us but are strongly antigenic to others
• One type of these, MHC proteins, mark a cell as self
• The two classes of MHC proteins are:
• Class I MHC proteins – found on virtually all body cells
• Class II MHC proteins – found on certain immune response
MHC Proteins
• Are coded for by genes of the major histocompatibility complex
(MHC) and are unique to an individual
• Each MHC molecule has a deep groove that displays a peptide,
which is a normal cellular product of protein recycling
• In infected cells, MHC proteins bind to fragments of foreign
antigens, which play a crucial role in mobilizing the immune system
Cells of the Adaptive Immune System
• Two types of lymphocytes
• B lymphocytes – oversee humoral immunity
• T lymphocytes – non-antibody-producing cells that constitute the
cell-mediated arm of immunity
• Antigen-presenting cells (APCs):
• Do not respond to specific antigens
• Play essential auxiliary roles in immunity
Lymphocytes
• Immature lymphocytes released from bone marrow are essentially
identical
• Whether a lymphocyte matures into a B cell or a T cell depends on
where in the body it becomes immunocompetent
• B cells mature in the bone marrow
• T cells mature in the thymus
T Cells and B Cells
• T cells mature in the thymus under negative and positive selection
pressures
• Negative selection – eliminates T cells that are strongly anti-self
• Positive selection – selects T cells with a weak response to self-
antigens, which thus become both immunocompetent and self-
tolerant
• B cells become immunocompetent and self-tolerant in bone marrow
Immunocompetent B or T cells
• Display a unique type of receptor that responds to a distinct antigen
• Become immunocompetent before they encounter antigens they may
later attack
• Are exported to secondary lymphoid tissue where encounters with
antigens occur
• Mature into fully functional antigen-activated cells upon binding
with their recognized antigen
• It is genes, not antigen, that determine which foreign substance our
immune system will recognize and resist
Antigen-Presenting Cells (APCs)
• Major rolls in immunity are:
• To engulf foreign particles
• To present fragment of antigens on their own surfaces, to be
recognized by T cells
• Major APCs are dendritic cells (DCs), macrophages, and activated
B cells
• The major initiators of adaptive immunity are DCs, which actively
migrate to the lymph nodes and secondary lymphoid organs and
present antigens to T and B cells
Macrophages and Dendritic Cells
• Secrete soluble proteins that active T cells
• Activated T cells in turn release chemicals that:
• Rev up the maturation and mobilization of DCs
• Prod macrophages to become activated macrophages, which are
insatiable phagocytes and release bactericidal chemicals
Adaptive Immunity: Summary
• Two-fisted defensive system that uses lymphocytes, APCs, and
specific molecules to identify and destroy nonself particles
• Its response depends upon the ability of its cells to:
• Recognize foreign substances (antigens) by binding to them
• Communicate with one another so that the whole system mounts a
response specific to those antigens
Humoral Immunity Response
• Antigen challenge – first encounter between and antigen and a naive
immunocompetent cell
• Takes place in the spleen or other lymphoid organ
• If the lymphocyte is a B cell:
• The challenging antigen provokes a humoral immune response
• Antibodies are produced against the challenger
Clonal Selection
• Stimulated B cell growth forms clones bearing the same antigen-
specific receptors
• A naive, immunocompetent B cell is activated when antigens bind
to its surface receptors and cross-link adjacent receptors
• Antigen binding is followed by receptor-mediated endocytosis of the
cross-linked antigen-receptor complexes
• These activating events, plus T cell interactions, trigger clonal
selection
Fate of the Clones
• Most clone cells become antibody-secreting plasma cells
• Plasma cells secrete specific antibody at the rate of 2000 molecules
per second
• Secreted antibodies:
• Bind to free antigens
• Mark the antigens for destruction by specific or nonspecific
mechanisms
• Clones that do not become plasma cells become memory cells that
can mount an immediate response to subsequent exposures to an
antigen
Immunological Memory
• Primary immune response – cellular differentiation and
proliferation, which occurs on the first exposure to a specific antigen
• Lag period: 3 to 6 days after antigen challenge
• Peak levels of plasma antibody are achieved in 10 days
• Antibody levels then decline
• Secondary immune response – re-exposure to the same antigen
• Sensitized memory cells respond within hours
• Antibody levels peak in 2 to 3 days at much higher levels than in the
primary response
 • Antibodies bind with greater affinity, and their levels in the blood
can remain high for weeks to months
Immunological Memory
Active Humoral Immunity
• B cells encounter antigens and produce antibodies against them
• Naturally acquired – response to a bacterial or viral infection
• Artificially acquired – response to a vaccine of dead or attenuated
pathogens
• Vaccines – spare us the symptoms of disease, and their weakened
antigens provide antigenic determinants that are immunogenic and
reactive
Passive Humoral Immunity
• Differs from active immunity in the antibody source and the degree
of protection
• B cells are not challenged by antigen
• Immunological memory does not occur
• Protection ends when antigens naturally degrade in the body
• Naturally acquired – from the mother to her fetus via the placenta
• Artificially acquired – from the injection of serum, such as gamma
globulin
Antibodies (Ab)
• Also called immunoglobulins (Igs)
• Constitute the gamma globulin portion of blood proteins
• Are soluble proteins secreted by activated B cells and plasma cells
in response to an antigen
• Are capable of binding specifically with that antigen
• There are five classes of antibodies: IgD, IgM, IgG, IgA, and IgE
Classes of Antibodies
• IgD – monomer attached to the surface of B cells, important in B
cell activation
• IgM – pentamer released by plasma cells during the primary
immune response
• IgG – monomer that is the most abundant and diverse antibody in
primary and secondary response; crosses the placenta and confers
passive immunity
• IgA – dimer that helps prevent attachment of pathogens to epithelial
cell surfaces
• IgE – monomer that binds to mast cells and basophils, causing
histamine release when activated
Basic Antibody Structure
• Consist of four looping polypeptide chains linked together with
disulfide bonds
• Two identical heavy (H) chains and two identical light (L) chains
• The four chains bound together form an antibody monomer
• Each chain has a variable (V) region at one end and a constant (C)
region at the other
• Variable regions of the heavy and light chains combine to form the
antigen-binding site
• Antibodies responding to different antigens have different V regions
but the C region is the same for all antibodies in a given class
• C regions form the stem of the Y-shaped antibody and:
• Determine the class of the antibody
• Serve common functions in all antibodies
• Dictate the cells and chemicals that the antibody can bind to
• Determine how the antibody class will function in elimination of
antigens
Mechanisms of Antibody Diversity
• Plasma cells make over a billion different types of antibodies
• Each cell, however, only contains 100,000 genes that code for these
polypeptides
• To code for this many antibodies, somatic recombination takes place
• Gene segments are shuffled and combined in different ways by each
B cell as it becomes immunocompetent
• Information of the newly assembled genes is expressed as B cell
receptors and as antibodies
Antibody Diversity
• Random mixing of gene segments makes unique antibody genes
that:
• Code for H and L chains
• Account for part of the variability in antibodies
• V gene segments, called hypervariable regions, mutate and increase
antibody variation
• Plasma cells can switch H chains, making two or more classes with
the same V region
Antibody Targets
• Antibodies themselves do not destroy antigen; they inactivate and
tag it for destruction
• All antibodies form an antigen-antibody (immune) complex
• Defensive mechanisms used by antibodies are neutralization,
agglutination, precipitation, and complement fixation
Complement Fixation and Activation
• Complement fixation is the main mechanism used against cellular
antigens
• Antibodies bound to cells change shape and expose complement
binding sites
• This triggers complement fixation and cell lysis
• Complement activation:
• Enhances the inflammatory response
• Uses a positive feedback cycle to promote phagocytosis
• Enlists more and more defensive elements
Other Mechanisms of Antibody Action
• Neutralization – antibodies bind to and block specific sites on
viruses or exotoxins, thus preventing these antigens from binding to
receptors on tissue cells
• Agglutination – antibodies bind the same determinant on more than
one antigen
• Makes antigen-antibody complexes that are cross-linked into large
lattices
• Cell-bound antigens are cross-linked, causing clumping
(agglutination)
• Precipitation – soluble molecules are cross-linked into large
insoluble complexes
Monoclonal Antibodies
• Commercially prepared antibodies are used:
• To provide passive immunity
• In research, clinical testing, and treatment of certain cancers
• Monoclonal antibodies are pure antibody preparations
• Specific for a single antigenic determinant
• Produced from descendents of a single cell
• Hybridomas – cell hybrids made from a fusion of a tumor cell and a
B cell
• Have desirable properties of both parent cells – indefinite
proliferation as well as the ability to produce a single type of
antibody
Cell-Mediated Immune Response
• Since antibodies are useless against intracellular antigens, cell-
mediated immunity is needed
• Two major populations of T cells mediate cellular immunity
• CD4 cells (T4cells) are primarily helper T cells (TH)
• CD8 cells (T8cells) are cytotoxic T cells (TC) that destroy cells
harboring foreign antigens
• Other types of T cells are:
 • Delayed hypersensitivity T cells (TDH)
• Suppressor T cells (TS)
• Memory T cells
Importance of Humoral and Cellular Responses
• Humoral Response
• Soluble antibodies
• The simplest ammunition of the immune response
• Interact in extracellular environments such as body secretions,
tissue fluid, blood, and lymph
• Cellular Response
• T cells recognize and respond only to processed fragments of
antigen displayed the surface of body cells
• T cells are best suited for cell-to-cell interactions, and target:
• Cells infected with viruses, bacteria, or intracellular parasites
• Abnormal or cancerous cells
• Cells of infused or transplanted foreign tissue
Antigen Recognition and MHC Restriction
• Immunocompetent T cells are activated when the V regions of their
surface receptors bind to a recognized antigen
• T cells must simultaneously recognize:
• Nonself (the antigen)
• Self (a MHC protein of a body cell)
MHC Proteins
• Both types of MHC proteins are important to T cell activation
• Class I MHC proteins
• Always recognized by CD8 T cells
• Display peptides from endogenous antigens
Class I MHC Proteins
• Endogenous antigens are:
• Degraded by proteases and enter the endoplasmic reticulum
• Transported via TAP (transporter associated
with antigen processing)
• Loaded onto class I MHC molecules
• Displayed on the cell surface in association with a class I MHC
molecule
Class II MHC Proteins
• Class II MHC proteins are found only on mature B cells, some T
cells, and antigen-presenting cells
• A phagosome containing pathogens (with exogenous antigens)
merges with a lysosome
• Invariant protein prevents class II MHC proteins from binding to
peptides in the endoplasmic reticulum
• Class II MHC proteins migrate into the phagosomes where the
antigen is degraded and the invariant chain is removed for peptide
loading
• Loaded Class II MHC molecules then migrate to the cell membrane
and display antigenic peptide for recognition by CD4 cells
Antigen Recognition
• Provides the key for the immune system to recognize the presence
of intracellular microorganisms
• MHC proteins are ignored by T cells if they are complexed with self
protein fragments
• If MHC proteins are complexed with endogenous or exogenous
antigenic peptides, they:
• Indicate the presence of intracellular infectious microorganisms
• Act as antigen holders
• Form the self part of the self-antiself complexes recognized by T
cells
T Cell Activation: Step One – Antigen Binding
• T cell antigen receptors (TCRs):
• Bind to an antigen–MHC protein complex
• Have variable and constant regions consisting of two chains (alpha
and beta)
• MHC restriction – TH and TC bind to different classes of MHC
proteins
• TH cells bind to antigen linked to class II MHC proteins
• Mobile APCs (Langerhans’ cells) quickly alert the body to the
presence of antigen by migrating to the lymph nodes and presenting
antigen
• TC cells are activated by antigen fragments complexed with class I
MHC proteins
• APCs produce costimulatory molecules that are required for
TC activation
• TCR that acts to recognize the self-antiself complex is linked to
multiple intracellular signaling pathways
• Other T cell surface proteins are involved in antigen binding (e.g.,
CD4 and CD8 help maintain coupling during antigen recognition)
T Cell Activation: Step Two – Costimulation
• Before a T cell can undergo clonal expansion, it must recognize one
or more costimulatory signals
• This recognition may require binding to other surface receptors on
an APC
• Macrophages produce surface B7 proteins when nonspecific
defenses are mobilized
• B7 binding with the CD28 receptor on the surface of T cells is a
crucial costimulatory signal
• Other costimulatory signals include cytokines and interleukin 1 and
2
• Depending upon receptor type, costimulators can cause T cells to
complete their activation or abort activation
• Without costimulation, T cells:
• Become tolerant to that antigen
• Are unable to divide
• Do not secrete cytokines
• T cells that are activated:
• Enlarge, proliferate, and form clones
• Differentiate and perform functions according to their T cell class
• Primary T cell response peaks within a week after signal exposure
• T cells then undergo apoptosis between days 7 and 30
• Effector activity wanes as the amount of antigen declines
• The disposal of activated effector cells is a protective mechanism for
the body
• Memory T cells remain and mediate secondary responses to the
same antigen
Cytokines
• Mediators involved in cellular immunity, including hormonelike
glycoproteins released by activated T cells and macrophages
• Some are costimulators of T cells and T cell proliferation
• Interleukin 1 (IL-1) released by macrophages costimulates bound T
cells to:
• Release interleukin 2 (IL-2)
• Synthesize more IL-2 receptors
• IL-2 is a key growth factor, which sets up a positive feedback cycle
that encourages activated T cells to divide
• It is used therapeutically to enhance the body’s defenses against
cancer
• Other cytokines amplify and regulate immune and nonspecific
responses
• Examples include:
• Perforin and lymphotoxin – cell toxins
• Gamma interferon – enhances the killing power of macrophages
• Inflammatory factors
Helper T Cells (TH)
• Regulatory cells that play a central role in the immune response
• Once primed by APC presentation of antigen, they:
• Chemically or directly stimulate proliferation of other T cells
• Stimulate B cells that have already become bound to antigen
• Without TH, there is no immune response
• TH cells interact directly with B cells that have antigen fragments on
their surfaces bound to MHC II receptors
• TH cells stimulate B cells to divide more rapidly and begin antibody
formation
• B cells may be activated without TH cells by binding to T cell–
independent antigens
• Most antigens, however, require TH costimulation to activate B cells
• Cytokines released by TH amplify nonspecific defenses
Cytotoxic T Cells (TC)
• TC cells, or killer T cells, are the only T cells that can directly attack
and kill other cells
• They circulate throughout the body in search of body cells that
display the antigen to which they have been sensitized
• Their targets include:
• Virus-infected cells
• Cells with intracellular bacteria or parasites
• Cancer cells
• Foreign cells from blood transfusions or transplants
• Bind to self-antiself complexes on all body cells
• Infected or abnormal cells can be destroyed as long as appropriate
antigen and costimulatory stimuli (e.g., IL-2) are present
• Natural killer cells activate their killing machinery when they bind
to MICA receptor
• MICA receptor – MHC-related cell surface protein in cancer cells,
virus-infected cells, and cells of transplanted organs
Mechanisms of TC Action
• In some cases, TC cells:
• Bind to the target cell and release perforin into its membrane
• Perforin causes cell lysis by creating transmembrane pores
• Other TC cells induce cell death by:
• Secreting lymphotoxin, which fragments the target cell’s DNA
• Releasing tumor necrosis factor (TNF), which triggers apoptosis
• Secreting gamma interferon, which stimulates phagocytosis by
macrophages
Other T Cells
• Suppressor T cells (TS) – regulatory cells that release cytokines,
which suppress the activity of both T cells and B cells
• Delayed-type hypersensitivity cells (TDH) – cells instrumental in
promoting allergic reactions called delayed hypersensitivity
reactions
• Gamma delta T cells – 10% of all T cells found in the intestines that
are triggered by binding to MICA receptors
Immunodeficiencies
• Congenital and acquired conditions in which the function or
production of immune cells, phagocytes, or complement is abnormal
• SCID – severe combined immunodeficiency (SCID) syndromes;
genetic defects that produce:
• A marked deficit in B and T cells
• Abnormalities in interleukin receptors
• Defective adenosine deaminase (ADA) enzymes
• Metabolites lethal to T cells accumulate
• SCID is fatal if untreated; treatment is with bone marrow transplants
Acquired Immunodeficiencies
• Hodgkin’s disease – cancer of the lymph nodes leads to
immunodeficiency by depressing lymph node cells
• Acquired immune deficiency syndrome (AIDS) – cripples the
immune system by interfering with the activity of helper T (CD4)
cells
• Characterized by severe weight loss, night sweats, and swollen
lymph nodes
• Opportunistic infections occur, including pneumocystis pneumonia
and Kaposi’s sarcoma
AIDS
• Caused by human immunodeficiency virus (HIV) transmitted via
body fluids – blood, semen, and vaginal secretions
• HIV enters the body via:
• Blood transfusions
• Contaminated needles
• Intimate sexual contact, including oral sex
• HIV:
• Destroys TH cells
• Depresses cell-mediated immunity
• HIV multiplies in lymph nodes throughout the asymptomatic period
• Symptoms appear in a few months to 10 years
• Attachment
• HIV’s coat protein (gp120) attaches to the CD4 receptor
 • A nearby protein (gp41) fuses the virus to the target cell
• HIV enters the cell and uses reverse transcriptase to produce DNA
from viral RNA
• This DNA (provirus) directs the host cell to make viral RNA (and
proteins), enabling the virus to reproduce and infect other cells
• HIV reverse transcriptase is not accurate and produces frequent
transcription errors
• This high mutation rate causes resistance to drugs
• Treatments include:
• Reverse transcriptase inhibitors (AZT)
• Protease inhibitors (saquinavir and ritonavir)
• New drugs that are currently being developed, which block HIV’s
entry to helper T cells
Autoimmune Diseases
• Loss of the immune system’s ability to distinguish self from nonself
• The body produces autoantibodies and sensitized TC cells that
destroy its own tissues
• Examples include multiple sclerosis, myasthenia gravis, Graves’
disease, Type I (juvenile) diabetes mellitus, systemic lupus
erythematosus (SLE), glomerulonephritis, and rheumatoid arthritis
Mechanisms of Autoimmune Disease
• Ineffective lymphocyte programming – self-reactive T and B cells
that should have been eliminated in the thymus and bone marrow
escape into the circulation
• New self-antigens appear, generated by:
• Gene mutations that cause new proteins to appear
• Changes in self-antigens by hapten attachment or as a result of
infectious damage
• Foreign antigens resemble self-antigens:
• Antibodies made against foreign antigens cross-react with self-
antigens
Hypersensitivity
• Immune responses that cause tissue damage
• Different types of hypersensitivity reactions are distinguished by:
• Their time course
• Whether antibodies or T cells are the principle immune elements
involved
• Antibody-mediated allergies are immediate and subacute
hypersensitivities
• The most important cell-mediated allergic condition is delayed
hypersensitivity
Immediate Hypersensitivity
• Acute (type I) hypersensitivities begin in seconds after contact with
allergen
• Anaphylaxis – initial allergen contact is asymptomatic but sensitizes
the person
• Subsequent exposures to allergen cause:
• Release of histamine and inflammatory chemicals
• Systemic or local responses
• The mechanism involves IL-4 secreted by T cells
• IL-4 stimulates B cells to produce IgE
• IgE binds to mast cells and basophils causing them to degranulate,
resulting in a flood of histamine release and inducing the
inflammatory response
Local Type I Responses
• Reactions include runny nose, itching reddened skin, and watery
eyes
• If allergen is inhaled, asthmatic symptoms appear – constriction of
bronchioles and restricted airflow
• If allergen is ingested, cramping, vomiting, and diarrhea occur
• Antihistamines counteract these effects
Systemic Response: Anaphylactic Shock
• Response to allergen that directly enters the blood (e.g., insect bite,
injection)
• Basophils and mast cells are enlisted throughout the body
• Systemic histamine releases may result in:
• Constriction of bronchioles
• Sudden vasodilation and fluid loss from the bloodstream
• Hypotensive shock and death
• Treatment – epinephrine is the drug of choice
Subacute Hypersensitivities
• Caused by IgM and IgG, and transferred via blood plasma or serum
• Onset is slow (1–3 hours) after antigen exposure
• Duration is long lasting (10–15 hours)
• Cytotoxic (type II) reactions
• Antibodies bind to antigens on specific body cells, stimulating
phagocytosis and complement-mediated lysis of the cellular
antigens
• Example: mismatched blood transfusion reaction
Subacute Hypersensitivities
• Immune complex (type III) hypersensitivity
• Antigens are widely distributed through the body or blood
 • Insoluble antigen-antibody complexes form
• Complexes cannot be cleared from a particular area of the body
• Intense inflammation, local cell lysis, and death may result
• Example: systemic lupus erythematosus (SLE)
Delayed Hypersensitivities (Type IV)
• Onset is slow (1–3 days)
• Mediated by mechanisms involving delayed hypersensitivity T cells
(TDH cells) and cytotoxic T cells (TC cells)
• Cytokines from activated TC are the mediators of the inflammatory
response
• Antihistamines are ineffective and corticosteroid drugs are used to
provide relief
• Example: allergic contact dermatitis (e.g., poison ivy)
• Involved in protective reactions against viruses, bacteria, fungi,
protozoa, cancer, and rejection of foreign grafts or transplants
Developmental Aspects
• Immune system stem cells develop in the liver and spleen by the
ninth week
• Later, bone marrow becomes the primary source of stem cells
• Lymphocyte development continues in the bone marrow and thymus
• TH2 lymphocytes predominate in the newborn, and the TH1 system
is educated as the person encounters antigens
• The immune system is impaired by stress and depression
• With age, the immune system begins to wane